DESCRIPTION: (Applicant's Abstract) The complex relationships between alcohol use, HCV disease, and HIV disease progression have not been well characterized. The co-occurrence of these conditions is common. Both alcohol and HIV infection accelerate the development of HCV complications. The impact of alcohol and HCV infection on the course of HIV infection is less clear. The objective of this project, the HIV Longitudinal Interrelationships of Viruses and Ethanol Study (the HIV-LIVE Study), is to test whether alcohol consumption and HCV, separately and together, are associated with worse HIV-related disease outcomes, and to determine the magnitude and importance of the effects. We will draw upon an existing cohort to enroll 400 subjects with both alcohol diagnoses and HIV infection from a diverse population with a HCV combined prevalence of 50 percent at Boston Medical Center and the Beth Israel-Deaconess Medical Center. The cohort will be assessed at baseline regarding alcohol diagnosis and consequences, recent and lifetime consumption, drug use and addiction severity, CD4 cell counts, HIV viral load, HCV antibody, viral RNA and genotype, liver disease, HIV disease severity, health-related quality of life, and comorbidity using standard measures. Subjects will be followed twice a year for 3.5 years to determine the primary outcomes, disease progression as determined by CD4 count and incident opportunistic infections. Additional outcomes include clinical progression of liver disease, acute care hospitalization, mortality, health-related quality of life, HIV viral load, and HIV and HCV medication use. Using data from this cohort and the literature, we will develop a comprehensive computer simulation model that will delineate the magnitude of impact that alcohol, HCV and other important determinants such as drug use, other comorbidity, antiretroviral therapy and opportunistic infection prophylaxis have on HIV disease progression. This HIV/HCV policy model will provide a framework for the understanding of the policy implications of a wide range of interventions and will allow the extrapolation of the cohort study data beyond the end of the study. The main hypotheses to be tested are that HCV-infected persons have worse HIV-related outcomes than those without HCV, hazardous alcohol consumption leads to worse HIV-related outcomes, and subjects with both HCV and alcohol diagnoses have the worst outcomes. The results of this study will provide crucial information needed for the development and prioritization of interventions for coinfected persons with addictions.